AU2015324111B2 - Processes and intermediates in the preparation of C5aR antagonists - Google Patents
Processes and intermediates in the preparation of C5aR antagonists Download PDFInfo
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- AU2015324111B2 AU2015324111B2 AU2015324111A AU2015324111A AU2015324111B2 AU 2015324111 B2 AU2015324111 B2 AU 2015324111B2 AU 2015324111 A AU2015324111 A AU 2015324111A AU 2015324111 A AU2015324111 A AU 2015324111A AU 2015324111 B2 AU2015324111 B2 AU 2015324111B2
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- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 239000000852 hydrogen donor Substances 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
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- 229910052740 iodine Inorganic materials 0.000 description 1
- ZCYVEMRRCGMTRW-YPZZEJLDSA-N iodine-125 Chemical compound [125I] ZCYVEMRRCGMTRW-YPZZEJLDSA-N 0.000 description 1
- 229940044173 iodine-125 Drugs 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 229940078552 o-xylene Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
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- 230000001575 pathological effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical class OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 231100000336 radiotoxic Toxicity 0.000 description 1
- 230000001690 radiotoxic effect Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
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- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Heart & Thoracic Surgery (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Vascular Medicine (AREA)
- Oncology (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Priority Applications (1)
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| AU2021204209A AU2021204209B2 (en) | 2014-09-29 | 2021-06-22 | Processes and intermediates in the preparation of C5aR antagonists |
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| US201462057107P | 2014-09-29 | 2014-09-29 | |
| US62/057,107 | 2014-09-29 | ||
| PCT/US2015/052697 WO2016053890A1 (fr) | 2014-09-29 | 2015-09-28 | Procédés et intermédiaires utilisés dans la préparation d'antagonistes de c5ar |
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| JP (1) | JP6898229B6 (fr) |
| KR (2) | KR20230149873A (fr) |
| CN (2) | CN113121415A (fr) |
| AU (2) | AU2015324111B2 (fr) |
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| CA (2) | CA3220371A1 (fr) |
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| SG172338A1 (en) | 2008-12-22 | 2011-07-28 | Chemocentryx Inc | C5ar antagonists |
| SI2585064T1 (sl) | 2010-06-24 | 2017-08-31 | Chemocentryx, Inc. | Antagonisti C5AR |
| ES2926828T3 (es) * | 2014-09-29 | 2022-10-28 | Chemocentryx Inc | Procesos e intermedios en la preparación de antagonistas de C5aR |
| US20170202821A1 (en) | 2016-01-14 | 2017-07-20 | Chemocentryx, Inc. | Method of treating c3 glomerulopathy |
| EP3703687A4 (fr) * | 2017-10-30 | 2021-04-07 | ChemoCentryx, Inc. | Composés deutérés utilisés comme immunomodulateurs |
| EP3801519A4 (fr) | 2018-06-07 | 2022-03-30 | ChemoCentryx, Inc. | Dosage et effet d'un antagoniste de c5a avec une vasculite associée aux anca |
| MA54318B1 (fr) | 2018-11-30 | 2023-08-31 | Chemocentryx Inc | Formulations de capsules |
| KR102207333B1 (ko) * | 2019-09-09 | 2021-01-27 | 성균관대학교산학협력단 | 4중 연속 고리 화합물의 신규한 제조방법 |
| BR112022007489A2 (pt) | 2019-11-08 | 2022-07-12 | Chemocentryx Inc | Forma amorfa de um receptor c5a de componente do complemento |
| KR20220098179A (ko) * | 2019-11-08 | 2022-07-11 | 케모센트릭스, 인크. | 보체 성분 C5a 수용체의 유리 염기 결정질 형태 |
| TW202128623A (zh) | 2019-11-08 | 2021-08-01 | 美商卡默森屈有限公司 | 補體成分Ｃ５ａ受體之鹽形式 |
| WO2022078269A1 (fr) * | 2020-10-16 | 2022-04-21 | 苏州科睿思制药有限公司 | Forme cristalline d'avacopan, son procédé de préparation et son utilisation |
| WO2022263263A1 (fr) | 2021-06-16 | 2022-12-22 | Sandoz Ag | Forme cristalline d'avacopan |
| EP4137133A1 (fr) | 2021-08-19 | 2023-02-22 | Sandoz AG | Forme cristalline d'avacopan |
| CN113957106B (zh) * | 2021-11-03 | 2024-04-19 | 暨明医药科技（苏州）有限公司 | 一种Avacopan及其中间体的制备方法 |
| CN114262291B (zh) * | 2022-01-04 | 2023-05-19 | 重庆医科大学 | 一种阿伐可泮的合成方法 |
| WO2023158722A2 (fr) | 2022-02-16 | 2023-08-24 | Teva Pharmaceuticals International Gmbh | Processus de préparation d'avacopan et de ses intermédiaires |
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| US4686100A (en) | 1985-04-02 | 1987-08-11 | The Board Of Trustees Of The Leland Stanford Junior University | Method for the treatment of adult respiratory distress syndrome |
| CN1261098C (zh) | 1998-08-28 | 2006-06-28 | 西奥斯股份有限公司 | p38－α激酶的抑制剂 |
| RU2197288C2 (ru) | 1999-08-03 | 2003-01-27 | Тверская медицинская академия | Способ лечения больных хроническим гломерулонефритом |
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| NZ523444A (en) * | 2000-06-29 | 2004-12-24 | Abbott Lab | Aryl phenylcyclopropyl sulphide derivatives and their use as cell adhesion-inhibiting anti-inflammatory and immune-suppressive agents |
| EP1308438B9 (fr) | 2000-08-10 | 2012-03-28 | Mitsubishi Tanabe Pharma Corporation | Derives d'uree substitues en position 3, et leur utilisation en medecine |
| CN102050758A (zh) | 2000-09-14 | 2011-05-11 | 田边三菱制药株式会社 | 酰胺衍生物及其制备药物的用途 |
| AU7622500A (en) | 2000-09-29 | 2002-07-01 | Neurogen Corp | High affinity small molecule c5a receptor modulators |
| SE524438C2 (sv) | 2000-10-05 | 2004-08-10 | Magnus Georg Goertz | Fjärrstyrt dörrelaterat låsarrangemang, första och andra datorpogramprodukt, bärande medium och ett datorlösbart medium |
| DE10293171D2 (de) | 2001-07-19 | 2004-07-01 | Luk Lamellen & Kupplungsbau | Ausrücksystem zur Betätigung einer Kupplung eines Fahrzeuges |
| ES2283594T5 (es) | 2001-08-17 | 2016-03-15 | Genentech, Inc. | Inhibidores de la ruta del complemento que se unen a C5 y C5a sin impedir la formación de C5b |
| MXPA04002662A (es) | 2001-09-21 | 2004-11-22 | Sanofi Aventis | Derivados de 3-substituida-4-pirimidona. |
| ITMI20012025A1 (it) | 2001-09-28 | 2003-03-28 | Dompe Spa | Sali di ammonio quaternari di omega-amminoalchilammidi di acidi r 2-aril-propionici e composizioni farmaceutiche che li contengono |
| US20030195192A1 (en) | 2002-04-05 | 2003-10-16 | Fortuna Haviv | Nicotinamides having antiangiogenic activity |
| EP1487796A4 (fr) | 2002-03-28 | 2005-11-16 | Neurogen Corp | Biarylamides substitues en tant que modulateurs du recepteur c5a |
| EP1487798A4 (fr) | 2002-03-28 | 2005-07-13 | Neurogen Corp | Tetrahydroisoquinoleines substituees servant de modulateurs du recepteur c5a |
| WO2003084524A1 (fr) | 2002-03-29 | 2003-10-16 | Neurogen Corporation | Therapie combinatoire pour le traitement de maladies faisant intervenir des composants inflammatoires |
| US20040014744A1 (en) | 2002-04-05 | 2004-01-22 | Fortuna Haviv | Substituted pyridines having antiangiogenic activity |
| CA2494942A1 (fr) * | 2002-08-08 | 2004-02-19 | Boehringer Ingelheim Pharmaceuticals, Inc. | Composes benzimidazole substitues |
| US7169775B2 (en) | 2002-08-21 | 2007-01-30 | Neurogen Corporation | Amino methyl imidazoles as C5a receptor modulators |
| FR2846654A1 (fr) | 2002-11-05 | 2004-05-07 | Servier Lab | Nouveaux derives de la 2,3-dihydro-4(1h)-pyridinone, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| AU2003290605A1 (en) | 2002-11-05 | 2004-06-03 | The Regents Of The University Of Michigan | Compositions and methods for the diagnosis and treatment of sepsis |
| AU2003291403A1 (en) | 2002-11-08 | 2004-06-03 | Neurogen Corporation | 3-substituted-6-aryl pyridined as ligands of c5a receptors |
| AU2003902354A0 (en) | 2003-05-15 | 2003-05-29 | Harkin, Denis W. | Treatment of haemorrhagic shock |
| BRPI0410630A (pt) | 2003-06-19 | 2006-06-13 | Pfizer Prod Inc | antagonista de nk1 |
| WO2005007087A2 (fr) | 2003-07-03 | 2005-01-27 | Neurogen Corporation | Derives (heterocycloalkyl)methyle substitues de type azole utilises comme modulateurs des recepteurs c5a |
| GB0325956D0 (en) | 2003-11-06 | 2003-12-10 | Addex Pharmaceuticals Sa | Novel compounds |
| NZ551603A (en) | 2004-06-24 | 2010-11-26 | Incyte Corp | N-substituted piperidines and their use as pharmaceuticals |
| EP1621536A1 (fr) * | 2004-07-27 | 2006-02-01 | Aventis Pharma S.A. | Dérivés d'urées cycliques aminés, leur préparation et utilisation pharmaceutique en tant qu'inhibiteurs de Kinase |
| US7635698B2 (en) | 2004-12-29 | 2009-12-22 | Millennium Pharmaceuticals, Inc. | Compounds useful as chemokine receptor antagonists |
| BRPI0607756A2 (pt) | 2005-02-18 | 2010-05-18 | Astrazeneca Ab | composto ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, método para inibição de dna girase bacteriana e/ou topoisomerase iv em um animal de sangue quente, uso de um composto ou um sal farmaceuticamente aceitável do mesmo, e, processo para preparar compostos ou sais farmaceuticamente aceitáveis dos mesmos |
| WO2007035428A1 (fr) | 2005-09-15 | 2007-03-29 | Bristol-Myers Squibb Company | Inhibiteurs de la kinase met |
| WO2007051062A2 (fr) | 2005-10-28 | 2007-05-03 | Chemocentryx, Inc. | Dihydropyridines substituees et leurs methodes d'utilisation |
| CA2629935C (fr) | 2005-11-24 | 2016-01-19 | Dompe S.P.A. | Derives (r)-arylalkylamines et compositions pharmaceutiques contenant ceux-ci |
| DK2359834T5 (en) | 2006-03-15 | 2017-02-06 | Alexion Pharma Inc | Treatment of paroxysmal nocturnal hemoglobinuria patients with a complement inhibitor |
| WO2008022060A2 (fr) | 2006-08-14 | 2008-02-21 | Novartis Ag | composés organiques et leurs utilisations |
| EP2077842A2 (fr) | 2006-10-31 | 2009-07-15 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Utilisation d'un antagoniste du récepteur egfr pour le traitement de la glomérulonéphrite |
| EP2178835A1 (fr) | 2007-06-29 | 2010-04-28 | Torrent Pharmaceuticals Ltd | Nouvelles pipéridones substituées en tant qu'inducteurs de hsp |
| US9284297B2 (en) | 2008-08-11 | 2016-03-15 | President And Fellows Of Harvard College | Halofuginone analogs for inhibition of tRNA synthetases and uses thereof |
| AU2009290137A1 (en) | 2008-09-03 | 2010-03-11 | Xenome Ltd | Libraries of peptide conjugates and methods for making them |
| US20100074863A1 (en) | 2008-09-17 | 2010-03-25 | Yat Sun Or | Anti-infective pyrrolidine derivatives and analogs |
| PT2894165T (pt) | 2008-11-10 | 2023-03-17 | Alexion Pharma Inc | Métodos e composições para o tratamento de distúrbios associados ao complemento |
| SG172338A1 (en) | 2008-12-22 | 2011-07-28 | Chemocentryx Inc | C5ar antagonists |
| WO2011035143A2 (fr) | 2009-09-17 | 2011-03-24 | The Regents Of The University Of Michigan | Procédés et compositions pour inhiber des maladies et des états à médiation par rho |
| SI2585064T1 (sl) * | 2010-06-24 | 2017-08-31 | Chemocentryx, Inc. | Antagonisti C5AR |
| CA2877526A1 (fr) | 2012-06-20 | 2013-12-27 | Novartis Ag | Modulateur de la voie d'activation du complement et ses utilisations |
| US20160060351A1 (en) | 2013-05-08 | 2016-03-03 | Novo Nordisk A/S | Use of C5AR Antagonists |
| ES2926828T3 (es) | 2014-09-29 | 2022-10-28 | Chemocentryx Inc | Procesos e intermedios en la preparación de antagonistas de C5aR |
| US20170202821A1 (en) | 2016-01-14 | 2017-07-20 | Chemocentryx, Inc. | Method of treating c3 glomerulopathy |
| NZ747259A (en) | 2016-04-04 | 2022-11-25 | Chemocentryx Inc | Soluble c5ar antagonists |
| KR20230124981A (ko) | 2020-12-21 | 2023-08-28 | 케모센트릭스, 인크. | C5a 억제제를 사용한 c3 사구체병증의 치료 |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110275639A1 (en) * | 2008-12-22 | 2011-11-10 | Chemocentryx, Inc. | C5aR ANTAGONISTS |
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